Many tumor-bearing animals develop antibodies to unique antigens associated with the oncogenic virus causing the tumor. These antigens, called "neoantigens," have been found in tumors caused by papovaviruses, adenoviruses, and herpes viruses. Hepatitis B virus, a hepadnavirus with suspected oncogenic potential, cannot be transmitted to non-primates but patients with HBV-associated hepatoma might be expected to have antibody to a HBV-associated neoantigen if one exists. Using a hepatoma cell line that contains integrated HBV DNA, we have sought immunofluorescent antibody in sera of hepatoma patients. Approximately seven percent of sera from HBsAg-positive hepatoma patients contain an antibody that reacts with a nuclear antigen in the hepatoma cell line. This antigen has been found in another hepatoma cell line that also contains integrated HBV genome but not in two other hepatoma cell lines lacking HBV genome. The antigen is being further characterized to determine if it is the product of a transforming gene.